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Abstract Background Effective provider-parent communication can improve childhood vaccination uptake and strengthen immunisation services in low- and middle-income countries (LMICs). Building capacity to improve communication strategies has been neglected. Rigorous research exists but is not readily found or applicable to LMICs, making it difficult for policy makers to use it to inform vaccination policies and practice. The aim of this project is to build research knowledge and capacity to use evidence-based strategies for improving communication about childhood vaccinations with parents and communities in LMICs. Methods and design This project is a mixed methods study with six sub-studies. In sub-study one, we will develop a systematic map of provider-parent communication interventions for childhood vaccinations by screening and extracting data from relevant literature. This map will inform sub-study two, in which we will develop a taxonomy of interventions to improve provider-parent communication around childhood vaccination. In sub-study three, the taxonomy will be populated with trial citations to create an evidence map, which will also identify how evidence is linked to communication barriers regarding vaccination. In the project's fourth sub-study, we will present the interventions map, taxonomy, and evidence map to international stakeholders to identify high-priority topics for systematic reviews of interventions to improve parent-provider communication for childhood vaccination. We will produce systematic reviews of the effects of high-priority interventions in the fifth sub-study. In the sixth and final sub-study of the project, evidence from the systematic reviews will be translated into accessible formats and messages for dissemination to LMICs. Discussion This project combines evidence mapping, conceptual and taxonomy development, priority setting, systematic reviews, and knowledge transfer. It will build and share concepts, terms, evidence, and resources to aid the development of communication strategies for effective vaccination programmes in LMICs.

Sounds produced by dolphins can be grouped into tonal (whistles) and pulsed sounds (e.g., echolocation clicks and burst sounds). Clicks are broadband pulses temporarily spaced to allow echo processing between the sound source and the object. Echolocation is related mainly to prey detection and environmental recognition. Echolocation click trains tend to present a decreasing inter-click interval due to a continuous changing of the target's location when the animal approaches to capture the prey. In addition to foraging and feeding contexts, burst pulsed sounds have been associated with short social communication. Although echolocation clicks are relatively well documented, there is no consensus regarding the broad variety of the burst pulsed signals. The present study analyzed time-frequency characteristics by conducting a clustering and discrimination analysis to classify pulsed sounds. A total of 64 click trains were analyzed from short-beaked common dolphins recorded in the slope region of the western South Atlantic Ocean. Three analyses (time; frequency; and combined time-frequency parameters) were compared through k-means clustering and posterior cluster validation using Random forest analysis. The k-means clustering resulted in four clusters for all groups of analysis. The time parameters were the most accurate among the comparisons, with the first two-dimensional axis corresponding to 87 % (Dim1 = 70.2 % and Dim2 = 17.2 %). The random forest analysis showed that the time-frequency dataset was the best classification of pulsed sounds in D. delphis (Accuracy = 84.6 %; confidence interval CI = 65.1 %-95.6 %; p < 0.01). This result considers the animal an acoustical identity, emphasizing the importance of certain parameters that influence this identity and thus reflecting the energy-cost optimization for sound production., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Severe alpha1 antitrypsin deficiency has been clearly associated with pulmonary emphysema, but its relationship with bronchial asthma remains controversial. Some deficient alpha 1 antitrypsin (AAT) genotypes seem to be associated with asthma development. The objective of this study was to analyze the distribution of AAT genotypes in asthmatic patients allergic to house dust mites (HDM), and to asses a possible association between these genotypes and severe asthma., Methods: A cross-sectional cohort study of 648 patients with HDM allergic asthma was carried out. Demographic, clinical and analytical variables were collected. PI*S and PI*Z AAT deficient alleles of the SERPINA1 gene were assayed by real-time PCR., Results: Asthma was intermittent in 253 patients and persistent in 395 patients (246 mild, 101 moderate and 48 severe). One hundred and forty-five asthmatic patients (22.4%) with at least one mutated allele (S or Z) were identified. No association between the different genotypes and asthma severity was found. No significant differences in all clinical and functional tests, as well as nasal eosinophils, IgA and IgE serum levels were observed. Peripheral eosinophils were significantly lower in patients with the PI*MS genotype (p = 0.0228). Neither association between deficient AAT genotypes or serum ATT deficiency (AATD) and development of severe asthma, or correlation between ATT levels and FEV1 was observed., Conclusion: In conclusion, the distribution of AAT genotypes in HDM allergic asthmatic patients did not differ from those found in Spanish population. Neither severe ATTD or deficient AAT genotypes appear to confer different clinical expression of asthma.

Context: The essential oil (EO) from Thymus capitatus Hoff. et Link. (Lamiaceae) has been traditionally used for its medicinal properties, such as anti-inflammatory, analgesic, antioxidant and antimicrobial properties., Objective: Characterize the constituents from T. capitatus EO and further evaluate the antinociceptive activity by in vivo and in vitro procedures., Materials and Methods: Gas chromatography-mass spectrometry was used to identify and quantify the constituents of the T. capitatus EO. The antinociceptive activity was evaluated in vivo by the glutamate-induced nociception model in male Swiss mice (25 g), at doses of 3, 6 and 12 mg/kg, 1 h before evaluation of the licking time response (0-15 min). The mechanism of T. capitatus EO (1-500 μg/mL) on the isolated nerve excitability of Wistar rat (300 g) was assessed by the single sucrose technique., Results and Discussion: The EO of T. capitatus presented 33 components, mainly monoterpenes and sesquiterpenes, carvacrol (ca. 80%) was its major constituent. T. capitatus EO induced antinociception in orally treated mice (3, 6, and 12 mg/kg) reducing the licking time from control (100.3 ± 11.9 s) to 84.8 ± 12.2, 62.7.6 ± 9.9, and 41.5 ± 12.7 s, respectively (n = 8; p < 0.05). Additionally, we have demonstrated that T. capitatus EO (500 μg/mL) decreased the compound action potential amplitude (V CAP ) of about 80.0 ± 4.3% from control recordings (n = 4; p < 0.05). Such activity was presumably mediated through a voltage-gated Na +  channels., Conclusions: The present study demonstrated the antinociceptive activity of Thymus capitatus essential oil, which acts via peripheral nervous excitability blockade.

A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action-wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro-protection, anti-epileptic, anxiolytic, anti-Alzheimer's disease, anti-Parkinson's disease, anti-cerebral ischemia, anti-neuropathic pain, anti-neuro-inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Acoustic parameters for the spinner dolphins' bioacoustic sounds have previously been described. However, the dolphins in the Southwest Atlantic Ocean were only recently studied near the Fernando de Noronha Archipelago. Therefore, to contribute to additional knowledge of this cosmopolitan species, this study compares previous results with a Brazilian recording. Despite statistically significant differences, the mean value comparison indicated that Hawaiian and Southwest Atlantic Ocean spinners emit similar whistles. The fact that geographical isolation does not lead the dissemblance nor the similarity of the acoustic variations in this species raises the possibility of other factors influencing those emissions. Here those differences and similarities are discussed, thereby contributing to an understanding of how distinct populations and/or species communicate through different ocean basins.

Acoustic parameters of killer whale (Orcinus orca) whistles were described for the western South Atlantic Ocean and highlight the occurrence of high frequency whistles. Killer whale signals were recorded on December of 2012, when a pod of four individuals was observed harassing a group of sperm whales. The high frequency whistles were highly stereotyped and were modulated mostly at ultrasonic frequencies. Compared to other contour types, the high frequency whistles are characterized by higher bandwidths, shorter durations, fewer harmonics, and higher sweep rates. The results add to the knowledge of vocal behavior of this species.

Matching molecularly targeted therapies with cancer subtype-specific gene mutations is revolutionizing oncology care. However, for rare cancers this approach is problematic due to the often poor understanding of the disease's natural history and phenotypic heterogeneity, making treatment of these cancers a particularly unmet medical need in clinical oncology. Advanced Sézary syndrome (SS), an aggressive, exceedingly rare variant of cutaneous T-cell lymphoma (CTCL) is a prototypical example of a rare cancer. Through whole genome and RNA sequencing (RNA-seq) of a SS patient's tumor we discovered a highly expressed gene fusion between CTLA4 (cytotoxic T lymphocyte antigen 4) and CD28 (cluster of differentiation 28), predicting a novel stimulatory molecule on the surface of tumor T cells. Treatment with the CTLA4 inhibitor ipilimumab resulted in a rapid clinical response. Our findings suggest a novel driver mechanism for SS, and cancer in general, and exemplify an emerging model of cancer treatment using exploratory genomic analysis to identify a personally targeted treatment option when conventional therapies are exhausted.

The literature shows that the monoterpenes are great candidates for the development of new drugs for the treatment of various pathological processes, including painful conditions. The gamma terpinene (γ-TPN) is a monoterpene present in plant species that have multiple pharmacological properties and has structural similarity to antinociceptive monoterpenes, such as limonene and alpha-phellandrene. The γ-TPN molecular mass was evaluated by mass spectrometry and showed a pseudomolecular ion with m/z 137.0 Da. The animals did not present any signs of acute toxicity at 2 g/kg, p.o. γ-TPN (1.562 to 50 mg/kg, p.o.) showed an antinociceptive effect in the formalin, capsaicin, and glutamate tests. γ-TPN has antinociceptive action when administered by others routes in glutamate test. To eliminate a possible sedative effect of γ-TPN, the open field and rota-rod test were conducted and the γ-TPN did not show muscle relaxant activity or central depressant effect. To investigate the mechanisms of action, the animals were pretreated with naloxone, glibenclamide, atropine, mecamylamine, or L-arginine in the glutamate test. γ-TPN antinociception was inhibited in the presence of naloxone, glibenclamide, atropine, and mecamylamine. The results suggest that the γ-TPN (p.o.) produced antinociceptive effect in models of chemical nociception through the cholinergic and opioid systems involvement.

Introduction: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains., Methods: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection., Results: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001)., Conclusions: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.

The plantain Plantago australis Lam. (Plantaginaceae) is a herbaceous species native to southern Brazil that is known for the analgesic, antibiotic, and anti-inflammatory properties of its leaf extracts (2). Powdery mildew was observed on wild P. australis plants in the cities of Tapejara, Jari, and Santa Maria (State of Rio Grande do Sul, Brazil) during the summer of 2011. Affected plants were more often observed in shaded areas. Signs included sparse to abundant white powdery masses of conidia and mycelium on pseudo-petioles and leaves, mostly on the adaxial surface. Severely affected plants (≥80% of foliar area affected) had small chlorotic leaves and reduced size compared to healthy ones. Mycelia were superficial and presented nipple-shaped appressoria. Conidiophores were often curved at the base, unbranched, cylindrical, 81 to 125 μm long (average 97.3 ± 14.9 μm) and composed of a cylindrical foot cell 52 to 73 μm long (average 65.4 ± 7.5 μm) and 9 to 14 μm wide (average 11.6 ± 1.5 μm) followed by one to two shorter cells 17 to 29 μm long (average 23.4 ± 3.6 μm). Conidia were produced in chains of up to eight cells, did not contain fibrosin bodies, ranged from ellipsoid-ovoid to subcylindrical, and measured 24 to 35 μm long (average 30.5 ± 3.7 μm) and 12 to 19 μm wide (average 15.8 ± 1.7 μm). Germ tubes were produced apically (reticuloidium type). Chasmothecia were not observed on sampled leaves. Genomic DNA was extracted from conidia, conidiophores, and mycelium and used to amplify the internal transcribed spacer (ITS) (ITS1-5.8s-ITS2) region using the ITS1 and ITS4 primers. The resulting sequence (558 bp) was deposited under accession number JX312220 in GenBank. Searches with the BLASTn algorithm revealed similarity of 100% with Golovinomyces orontii (Castagne) V.P. Heluta 1988 from Veronica arvensis L. (AB077652.1) (3), 99% with G. orontii from Galium spurium L. and Galium aparine L. (AB430818.1 and AB430813.1) (2) and 99% with G. sordidus (L. Junell) V.P. Heluta 1988 from P. lanceolata L. (AB077665.1) (3). Based on morphological characteristics and sequence analysis of the ITS region, the fungus was identified as belonging to Golovinomyces sp. To fulfill Koch's postulates, five cultivated plants of P. australis with four to five expanded leaves were inoculated by dusting conidia (10 to 15 conidia cm -2 ) on their leaves. Inoculated and non-inoculated control plants were kept in a greenhouse at 27 ± 5°C and relative humidity of 80 ± 15%. Powdery mildew symptoms identical to those of wild plants were observed 8 to 10 days after in inoculated plants. Although G. sordidus was previously reported on P. australis subsp. hirtella in Argentina and on several species of Plantago in others world regions (1), to our knowledge, Golovinomyces sp. has not been previously reported as a pathogen of P. australis in Brazil. Although the economic impact of the disease is limited, the reduction in plant size and leaves affects biomass production used in the extraction of pharmaceutical compounds. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series 11, 2012. (2) G. C. Sousa et al. J. Ethnopharmacol. 90:135, 2004. (3) S. Takamatsu et al. Mycol. Res. 113:117, 2009.

Flamboyant (Delonix regia) is an ornamental tree that is native to Madagascar and frequently used in gardens and parks worldwide. Powdery mildew was observed on flamboyant plants in the cities of Piracicaba and São Carlos (State of São Paulo, Brazil) during the springs of 2010 and 2011. All sampled plants (~15 plants) were affected by the disease. Affected plants had abundant, white powdery masses of conidia and mycelium on floral buds that is typical of powdery mildew, but these structures were not observed on leaves and petioles. Diseased buds were observed at all developmental stages. The fungus was identified as Erysiphe quercicola on the basis of scanning electron microscopy, light microscopy, and sequence analysis of the internal transcribed spacer (ITS) region. Conidia were produced in short chains of four to five spores on erect conidiophores. Conidiophores were unbranched, cylindrical, 50 to 80 μm long (mean 68.8 ± 10.8 μm), composed of a cylindrical foot cell 25 to 40 μm long (mean 32.2 ± 4.9 μm), and one to two shorter cells. Conidia were ellipsoid-ovoid to subcylindrical, 22 to 37 μm long (mean 30.9 ± 4.4 μm), and 10 to 18 μm wide (mean 15.1 ± 2.8 μm). Germ tubes were produced apically and ended in a lobed appressorium. Colonizing hyphae also had a well-developed lobed appressorium. Chasmothecia were not observed on buds. DNA was extracted from conidia, conidiophores, and mycelium and used to amplify the ITS (ITS1-5.8s-ITS2) region using the ITS1 and ITS4 primers (2) and its sequence (612 nt) was deposited under Accession No. JQ034229 in the GenBank. Searches with the BLASTn algorithm revealed 100% similarity with E. quercicola from oak (Accession Nos. AB292693.1, AB292691.1, and AB292690.1) (1). To fulfill Koch's postulates, 10 detached young floral buds, 0.4 to 0.8 cm in diameter, were inoculated with five to eight conidia collected on floral buds using an eyelash brush. Inoculated buds were placed on moistened filter paper in petri dishes. The negative control consisted of noninoculated young floral buds. Inoculated and noninoculated buds were incubated in a growth chamber at 25°C and a 12-h photoperiod. Powdery mildew structures were observed 6 to 8 days after inoculation. To our knowledge, E. quercicola has not been reported previously as a pathogen of flamboyant tree since there is no record in the Erysipahales database ( http://erysiphales.wsu.edu/ ). Although the economic impact of the disease is limited, its incidence might induce the abortion of floral buds and accelerate the senescence of flowers, thus reducing the aesthetic value of the trees. References: (1) S. Takamatsu et al. Mycol Res. 111:809, 2007. (2) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

Given the movement of medical specialists across borders in recent years, and the changes in legislation affecting the structure and operation of boards responsible for the various medical specialties, the task of harmonizing the training of respiratory medicine residents across the European Union has become crucial. The project for Harmonized Education in Respiratory Medicine for European Specialists (HERMES) is a collective response to this need. After 3 years of work toward building consensus, HERMES is entering its second phase. The Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has the aim of informing our resident trainees, their instructors, and others concerned with postgraduate education in respiratory medicine in Spain about this undeniably difficult task of harmonization.

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (beta-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.

Introduction: It has been hypothesized that medical procedures performed in high-volume units carry less risk and achieve a better outcome., Objective: To determine the relationship between the number of interventions and the operative morbidity, mortality and long-term survival in the surgery of bronchogenic carcinoma (BC)., Patients and Method: Prospective, multicenter Spanish study was conducted in 19 departments of thoracic surgery on 2994 patients operated on consecutively with the aim of curing BC. The thoracic surgery departments have been classified into three groups, according to the number of interventions performed per year: I (1-43 cases/year; centers=7; n=565; 18.9%), II (44-54 cases/year; centers=6; n=1044; 34.9%) and III (55 or more cases/year; centers=6; n=1385; 46.3%)., Results: When the three groups were compared, the frequency of complete surgery was found to be 84% for group I, 76% for group II and 83% for group III (p=0.001, for comparisons between groups I/II and II/III). The pathological stages were identical in the three groups. The overall morbidity and the mortality in all patients or above the age of 75 or in pneumonectomies were not different among the groups. When considering all the patients with prognostic information (n=2758), no differences were found regarding the 5-year survival among the groups. When only patients in postoperative stage I-II and complete resection were evaluated, excluding operative mortality (n=1128), 5-year survival was 0.58 for group I, 0.57 for group II and 0.50 for group III (p=0.06 between groups II and III; p=0.08 between groups I and III)., Conclusions: No significant differences that do not favor the hypothesis that there is increased surgical risk and worse survival in centers having a lower volume were found in this Spanish multicenter study.

Severe community-acquired pneumonia (CAP) is a life-threatening condition that requires intensive care unit (ICU) admission. Clinical presentation is characterized by the presence of respiratory failure, severe sepsis, or septic shock. Severe CAP accounts for approximately 5-35% of hospital-treated cases of pneumonia with the majority of patients having underlying comorbidities. The most common pathogens associated with this disease are Streptococcus pneumoniae, Legionella spp., Haemophilus influenzae, and Gram-negative enteric rods. Microbial investigation is probably helpful in the individual case but is likely to be more useful for defining local antimicrobial policies. The early and rapid initiation of empiric antimicrobial treatment is critical for a favorable outcome. It should include intravenous beta-lactam along with either a macrolide or a fluoroquinolone. Modifications of this basic regimen should be considered in the presence of distinct comorbid conditions and risk factors for specific pathogens. Other promising nonantimicrobial new therapies are currently being investigated. The assessment of severity of CAP helps physicians to identify patients who could be managed safely in an ambulatory setting. It may also play a crucial role in decisions about length of hospital stay and time of switching to oral antimicrobial therapy in different groups at risk. The most important adverse prognostic factors include advancing age, male sex, poor health of patient, acute respiratory failure, severe sepsis, septic shock, progressive radiographic course, bacteremia, signs of disease progression within the first 48-72 hours, and the presence of several different pathogens such as S. pneumoniae, Staphylococcus aureus, Gram-negative enteric bacilli, or Pseudomonas aeruginosa. However, some important topics of severity assessment remain controversial, including the definition of severe CAP. Prediction rules for complications or death from CAP, although far from perfect, should identify the majority of patients with severe CAP and be used to support decision-making by the physician. They may also contribute to the evaluation of processes and outcomes of care for patients with CAP.

Background: Extended cervical mediastinoscopy (ECM) is a technique in the staging of bronchogenic carcinoma described first by Ginsberg in 1984. To update our experience we have prospectively evaluated our results on 106 patients who underwent the technique from 1985 to 1998., Methods: The ECM technique is performed once the operability of the patient has been evaluated, according to the computed tomography findings. The intervention is carried out at the same time as a standard cervical mediastinoscopy through the same incision following the same technique as previously published. The ECM is considered positive when metastatic nodes or tumor involvement directly in the paraaortic or subaortic regions is detected and confirmed histologically. Negative cases of ECM and positive cases of standard cervical mediastinoscopy are excluded from this study. A false-negative ECM is defined as the presence of infiltrated adenopathies at the paraortic level detected on postoperative histologic study., Results: We had performed ECM in 106 patients, and a total of 13 were subsequently excluded for the reasons stated above. Of the remaining cases, 26 were positive, 61 negative and 6 had false-negative results with no false-positive results. Sensitivity was 81.2%, specificity 100%, accuracy 93.3%, positive predictive value 100%, and negative predictive value 91%. There were no complications with the technique., Conclusions: We conclude that ECM is a useful technique for staging bronchogenic carcinoma that allows samples to be taken from paraortic and subaortic regions with minimally invasive techniques.

Background: Several HLA alleles have been associated with asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid reactions, has not been established., Objective: The purpose of our work was to study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and anaphylactoid reactions caused by NSAIDs., Methods: We have analyzed 114 HLA DRB1 and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by NSAIDs, 47 patients who had exclusively cutaneous reactions during single-blind, placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA-DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence-specific primers method with genomic DNA., Results: The frequency of HLA-DR11 alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8-19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1; P <.004). No differences were observed among HLA-DR11 alleles analyzed. There were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid reactions. Patients with cutaneous reactions had HLA frequencies that did not differ significantly from the tolerant control subjects., Conclusion: The HLA-DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid reactions.

: BACKGROUND: Nosocomial pneumonia (NP) is a common complication in mechanically-ventilated patients and is considered to be one of the most common causes of morbidity and mortality. However, assessment of the associated mortality is not staightforward as it shares several risk factors with NP that confound the relationship. The aim of this study was to evaluate the impact of NP on the mortality rate in an intensive care unit. During the study period (January-December 1995) all patients under mechanical ventilation for a period > 48 h (n = 314) were prospectively evaluated, and the prognostic factors of NP, which have been identified in previous studies, were recorded. RESULTS: Pneumonia was diagnosed in 82 patients. The overall mortality rate was 34% for patients with NP compared to 17% in those without NP. Multivariate analysis selected the following three prognostic factors as being significantly associated with a higher risk of death: the presence of multiple organ failure [odds ratio (OR) 6.71, 95% CI, P < 0.001]; the presence of adult respiratory distress syndrome (ARDS) (OR 3.03, 95% CI, P < 0.01), and simplified acute physiology score (SAPS)> 9(OR 2.89, 95% CI, P < 0.05). CONCLUSIONS: In mechanically-ventilated patients NP does not represent an independent risk factor for mortality. Markers of severity of illness were the strongest predictors for mortality.

Background: Schnitzler's syndrome is a rare disorder characterized by chronic urticaria and monoclonal IgM gammopathy. The mechanisms of the urticarial flares remain poorly understood., Objective: To more accurately define the histopathologic changes in urticarial lesions, we reviewed 25 original biopsies from 15 cases of Schnitzler's syndrome, 11 of which have previously been reported., Results: Thirteen specimens from 9 patients showed urticaria with neutrophils (neutrophilic urticaria). Necrotizing leukocytoclastic vasculitis with positive immunofluorescence studies was found only in 2 biopsies from 1 patient who was genetically deficient in C4. Five specimens showed lymphocytic urticaria. Four biopsies demonstrated a spongiotic dermatitis; an eosinophilic spongiosis was seen in 2 biopsies from a patient who later developed pemphigus vulgaris. Epidermal changes were seen in 17 specimens from 10 patients., Conclusions: The histopathologic findings in Schnitzler's syndrome are not uniform although most cases demonstrated neutrophilic urticaria. Neutrophils in Schnitzler's syndrome are not usually related to immune complex vasculitis. Epidermal changes in Schnitzler's syndrome need to be further analyzed.

Significant cutaneous vascular IgA deposits are common in Henoch-Schönlein purpura but not in other vasculitides. The specificity for IgA vascular deposits for Henoch-Schönlein purpura is not well defined. To examine the specificity of IgA vascular deposits for this disease, we compared clinicopathologic features of 92 cases with IgA vascular deposits and a direct immunofluorescence impression of vasculitis with 90 similar cases without IgA deposits. Henoch-Schönlein purpura was diagnosed in 24% of cases with vascular IgA deposits on direct immunofluorescence examination. IgA deposits were frequent in erythema nodosum and venous stasis-related problems and in cryoglobulinemia, coagulopathic vasculopathies, and livedoid vasculitis. Of our cases, 78% exhibited vascular fluorescence with multiple conjugates. No histologic or immunofluorescence pattern alone was specific. The diagnostic specificity for Henoch-Schönlein purpura is improved if gastrointestinal involvement, upper respiratory infection, or age < 20 years is present. We propose diagnostic criteria for Henoch-Schönlein purpura incorporating clinical findings yielding sensitivity and specificity > 90%.

We assessed omental revascularization of heterotopic tracheal implants in rats, and investigated the influence of factors that can enhance revascularization. The trachea of the donor animal was excised in two parts, and each tracheal allograft was implanted in the omentum of two recipients. The influence of mechanical factors was evaluated by applying traction at both ends of the graft with and without drainage of the tracheal lumen, and the influence of pharmacologic factors by giving cefonicid, hydrocortisone, cefonicid plus hydrocortisone, or cyclosporine and azathioprine during the postoperative period. Revascularization of the graft from the omentum with preservation of the tracheal structure was established. Graft viability showed significant differences between the tracheal implants to which no traction had been applied and those with traction at both ends. Tracheal allografts from animals receiving immunosuppressants were completely viable and no significant differences were found between the controls and animals in this group.

Allergy to mollusk has rarely been described. The limpet, belonging to Phylum mollusca, is one of the most frequent mollusks in the Canary Islands, as in all warm maritime regions. We report two cases of atopic patients who developed anaphylactic reactions after ingestion of this mollusk. Type I hypersensitivity to limpet antigens was demonstrated by means of immediate skin test reactivity, specific IgE determination by RAST, and histamine release test to cooked limpet extract. The controls did not react to any of these tests. Allergic activity was only found with a cooked limpet extract; this suggests that the offending antigen/s may have been released by cooking this food.

The efferent activity of the short ciliary nerves was studied in 23 anesthetized cats. Spontaneous activity was recorded in all preparations, and 33% showed a rhythmic discharge. Ipsilateral common carotid occlusion (ICCO) at constant intraocular and arterial pressures changed the discharge frequency in 14 of 33 filaments. Of these, 13 filaments showed a decrease in their firing frequency whereas in only one the discharge increased. Contralateral common carotid occlusion (CCCO), at constant intraocular pressure, changed the firing frequency in 8 of 20 filaments: 5 of them showed a decrease in their discharge frequency, whereas in 3 of them the discharge increased. This occurred when systemic arterial pressure was allowed to increase. These results suggest the presence of an efferent pathway involved in the nervous modulation or control of intraocular blood flow, aqueous humor dynamics, and/or intraocular pressure.